Abstract
Currently, there is no effective antiviral medication for coronavirus disease 2019 (COVID-19) and the knowledge on the potential therapeutic target is in great need. Guided by a time-course transmission electron microscope (TEM) imaging, we analyzed early phosphorylation dynamics within the first 15 min during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry. Based on alterations in the phosphorylation events, we found that kinase activities such as protein kinase C (PKC), interleukin-1 receptor-associated kinase 4 (IRAK4), MAP/microtubule affinity-regulating kinase 3 (MARK3), and TANK-binding kinase 1 (TBK1) were affected within 15 min of infection. Application of the corresponding kinase inhibitors of PKC, IRAK4, and p38 showed significant inhibition of SARS-CoV-2 replication. Additionally, proinflammatory cytokine production was reduced by applying PKC and p38 inhibitors. By an acquisition of a combined image data using positive- and negative-sense RNA probes, as well as pseudovirus entry assay, we demonstrated that PKC contributed to viral entry into the host cell, and therefore, could be a potential COVID-19 therapeutic target.
Original language | English |
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Pages (from-to) | 112-121 |
Number of pages | 10 |
Journal | CCS Chemistry |
Volume | 4 |
Issue number | 1 |
Early online date | 3 Mar 2021 |
DOIs | |
Publication status | Published - 1 Jan 2022 |
Scopus Subject Areas
- General Chemistry
User-Defined Keywords
- Antiviral target
- Early responsive kinase
- Phosphoproteomics
- PKC
- SARS-CoV-2
- Viral entry